We will attempt to isolate a factor from the plasma of plasminogen- depleted cats which stimulates plasminogen production in recipients and explore techniques for depleting plasminogen by extracorporeal circulation. The fragment of streptokinase (SK) which is lost when SK of 33,000 M.W. (active) is converted by dog plasmin to SK of 25,700 M.W. (inactive) will be studied along with the residual SK molecule. If successful, these experiments should offer important clues to the understanding of SK activity at a molecular level. We will develop a quantitative, specific assay for circulating blood activator based on casein hydrolysis in a purified system and use this procedure to isolate the activator, study its mechanism of action and identify factors which affect the plasminogen activator blood level.